Surveillance & Research

Reducing vaccine preventable diseases in children: using national active hospital-based surveillance to evaluate and improve immunisation program performance

We are pleased to announce the award of our NHMRC-funded Partnership Project (APP1113851). This project is aimed at improving immunisation programs to most effectively and equitably prevent illness and death due to the two most prevalent vaccine preventable diseases in Australian children, influenza and pertussis.

Morbidity from influenza and pertussis remains a significant challenge. An average of 2,700 children are hospitalised from these diseases each year. Deaths also continue to occur from influenza and pertussis, even in previously healthy children and babies.

We will be undertaking a novel and systematic examination of how factors related to both the effectiveness and the uptake of vaccination contribute to controlling influenza and pertussis in Australian children.

This project expands upon our national partnership of major paediatric hospitals in Australia: the Paediatric Active Enhanced Disease Surveillance (PAEDS) network. We have established PAEDS sites in the major paediatric hospitals in five states (NSW, Western Australia, South Australia, Queensland and Victoria), and will be adding a sixth site in Darwin in the Northern Territory. With total funding comprising of fifty-per cent support from the NHMRC and fifty-per cent from our funding partners, who are all relevant State and Territory and the Australian Government Departments of Health, our collaboration is well placed to conduct this cutting edge program-relevant research.

Our nationally representative team is comprised of immunisation and public health experts, epidemiologists and social scientists. Over the coming three years we will undertake a range of studies, including:

a) identifying in whom breakthrough disease occurs despite immunisation and why, and we will estimate vaccine effectiveness of new programs;

b) identify reasons for under or no-vaccination at the individual, community, system and policy levels; and

c) determine factors or gaps in immunisation policy and practice that can be changed to improve prevention of disease from influenza and pertussis in children.

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Surveillance is ongoing for the three conditions monitored by PAEDS since 2007 – acute flaccid paralysis, intussusception and varicella/herpes zoster. Since then, additional conditions have been added to ongoing surveillance including – pertussis (2012), acute childhood encephalitis (2013) and influenza (2014).

In previous years, PAEDS has also studied important conditions such as pandemic influenza in 2009 and Guillain-Barré syndrome following pandemic influenza vaccine. Surveillance of febrile seizures (2013-2014) was also conducted following introduction of the new vaccines to the National Immunisation Program.

Pertussis

Pertussis is one of the most common vaccine-preventable diseases seen in Australia, with a recent large outbreak experienced nationally from 2008 to 2011, and again more recently in 2015. Pertussis is particularly severe in young infants, not yet fully immunised in whom many complications, and sometimes death, occur. PAEDS conducts surveillance for hospitalised pertussis in Australia, with special emphasis on disease severity, the need for intensive care, death and disability.

This work also aims to examine the contribution of co-infections and other co-morbidities, and disease transmission in households (by checking the immunisation history of patients, family members and ‘coughing contacts’).

These factors will also be correlated with the genetic sub-types identified in Bordetella pertussis positive cultures. Recruitment commenced in January 2012.

Febrile seizures

Febrile seizures typically occur in children from 6 months to 6 years of age and can be triggered by a sudden fever from any cause – most often from a viral illness. About 1 in 30 children of this age will have a febrile seizure, with recurrent seizures occurring in approximately one-third of children.

New vaccines recently added to the National Immunisation Program (the 13-valent pneumococcal conjugate vaccine and the combined measles-mumps-rubella-varicella vaccine) have been associated with somewhat high rates of fever, and therefore potentially a risk of febrile seizure occurring.

This PAEDS study will gather enhanced clinical and epidemiological information on febrile seizures and will determine if there is an increased risk of febrile seizures with these new vaccines. It will also describe the clinical and revaccination outcomes of children who have experienced a febrile seizure.

In addition, in four PAEDS sites, children who experience febrile seizures can enrol in an NHMRC funded study led by Dr Nicholas Wood from NCIRS, to look at genetic susceptibility to seizures and long term developmental outcomes. PAEDS surveillance for febrile seizures was conducted in 2013-2014.

Acute flaccid paralysis

Surveillance for acute flaccid paralysis (AFP) has been conducted by PAEDS since 2007. To retain polio free status in Australia, it is important that AFP surveillance meets World Health Organization requirements related to case identification, stool collection and case investigation.

PAEDS centres continue to notify most of the AFP cases that are reported in Australia to the Polio Expert Panel of the Department of Health and provide stool samples to the Victorian Infectious Diseases Reference Laboratory for testing for enteric pathogens. A recent review of Polio Surveillance in Australia confirmed the importance of PAEDS surveillance for AFP.

Acute childhood encephalitis

Encephalitis is a complex neurological syndrome caused by inflammation of the brain. Children are among those most severely affected.

However, there is limited knowledge about the causes of encephalitis in children worldwide and a cause is not found in up to 70% of cases using routine testing.

Australia has unique viruses and other infectious agents that potentially cause encephalitis. There is also increasing awareness of immune-mediated causes of encephalitis, but these have not been systematically studied in children.

The Australian Childhood Encephalitis study, led by Professor Cheryl Jones and Dr Philip Britton, aims to describe the incidence, aetiology, clinical characteristics, potential risk factors and short-term outcomes among Australian children hospitalised for encephalitis.

A 6-month pilot of surveillance for this complex condition began in 2013 at The Children's Hospital at Westmead site only, with roll-out to other states from early 2014.

To date, this study has shown considerable success in better understanding acute encephalitis and its causes as well as demonstrating the effectiveness of syndromic surveillance using the PAEDS system in identifying outbreaks related to emerging infectious diseases in children.

Influenza

From 2014, two PAEDS sites – The Children’s Hospital at Westmead (Sydney) and Princess Margaret Hospital (Perth) – have participated in active hospital-based surveillance for influenza with FluCAN (the Influenza Complications Alert Network). FluCAN is a rapid alert system for severe respiratory illness that commenced in 2009 and maintains a real-time sentinel hospital surveillance system for acute respiratory disease requiring hospitalisation. It currently operates across approximately 15 hospitals and has mainly assessed influenza in adult patients. Given the high burden of influenza in children, this collaboration between PAEDS and FluCAN promises to provide much needed, enhanced data on the complications of influenza in children, as well as assess vaccine effectiveness in this age group.

Intussusception

PAEDS has conducted surveillance for intussusception (IS) since 2007 when rotavirus vaccines (a potential trigger for IS) were introduced in Australia. PAEDS investigators were the first worldwide to publish data on the risk of IS associated with these new vaccines (Buttery et al. Vaccine 2011). This risk remains very low, however, in comparison with the benefits seen from rotavirus vaccination in Australia and worldwide.

Our PAEDS study was key in informing advice from the World Health Organization and other key expert bodies worldwide regarding the use of rotavirus vaccines. In 2012, a study commissioned by the Therapeutic Goods Administration (TGA) extended the analysis done by PAEDS. This study (Carlin et al. CID 2013), using data collected by many Australian states and territories in addition to PAEDS data, estimated that there would be approximately 6 additional cases of IS among every 100,000 infants vaccinated, or 14 additional cases per year in Australia.

Varicella and herpes zoster

Varicella vaccine was included on the National Immunisation Program in 2005 for all children at age 18 months, with catch-up vaccination via school-based programs. PAEDS has been conducting surveillance for hospitalised varicella since 2007. Information is collected on complications of chickenpox (varicella-zoster virus infection) and children hospitalised with shingles (herpes zoster). An important and unique aspect of this surveillance is that genotyping of the virus is also undertaken. Given that varicella has not been nationally notifiable in Australia, this surveillance has made an important contribution toward demonstrating the impact of the varicella vaccination program on severe disease.

In 2013, PAEDS published the first major study (Marshall et al. PIDJ 2013) to show a decline in hospitalised varicella and herpes zoster – estimated at 73% and 40%, respectively – since vaccine program commencement. In addition, all genotypes were ‘wild-type’ virus with no hospitalised cases due to any genotypes associated with the varicella vaccine. Of hospitalised children age-eligible for varicella vaccine, 80% were unimmunised, including all cases requiring intensive care. This reinforces the importance of vaccination. Surveillance for varicella is ongoing.